5613354 SCREENING FOR CEREBROVASCULAR DISEASE IN CHILDREN WITH SICKLE CELL DISEASE USING TRANSCRANIAL DOPPLER AND MRA TO PREVENT STROKE: THE AMSTERDAM COHORT
Authors: L.A. de Ligt, C.L. Eckhardt, K. Fijnvandraat, H. Heijboer
Journal: HemaSphere (2023)

Background: Cerebrovascular complications are the most devastating complications in patients with Sickle Cell Disease (SCD). To identify patients at risk of a first cerebrovascular accident (CVA), the American Society of Hematology (ASH) 2020 guideline for SCD recommends annual transcranial Doppler ultrasonography (TCD) screening for children aged 2-16 years with HbSS or HbSβ0 thalassemia. When abnormal TCD velocities are detected, chronic transfusion therapy is advised for at least a year.(1) Since 2000 we have implemented a different management protocol in Amsterdam that only prescribes transfusion therapy for children with confirmed MRA abnormalities when increased flow is present on TCD measurement. This Amsterdam protocol reduces exposure to chronic blood transfusions but we need to investigate the safety and efficacy. Methods: In this longitudinal single center cohort study, all patients managed according to the Amsterdam Protocol between January 2000 and September 2022 were included. TCD screening was performed in children with genotypes SS or Sβ0-thalassemia at a frequency of twice a year in the age group 4-10 years and annually in children aged 10 to 18 years. From January 1st 2010 onwards, screening was already initiated at the age of 2 years. When TCD screening demonstrated abnormal results at 2 separate assessments, magnetic resonance angiography (MRA) was performed. We only started chronic transfusion therapy in patients with a stenotic lesion present on MRA. In patients without abnormalities on MRA follow-up by TCD according to protocol was continued. Results: A total of 209 SCD patients were included in this study, cumulative 2874.5 patient-years of follow-up. The median age of these patients at the start of the follow-up was 0.74 (IQR: 0.0, 5.5) years. In this cohort, 30 patients had abnormal TCD results at 2 separate assessments. In all of these patients MRA was performed, which showed abnormal results in 16 cases. None of the 12 patients with abnormal TCD results and normal MRA results who did not receive chronic transfusion therapy developed a CVA. The total follow-up duration after the first abnormal TCD in these patients was 112.0 patient-years. Nine out of the 14 patients (64%) who had abnormal TCD results used hydroxyurea. The median time between the first abnormal TCD and initiation of hydroxyurea therapy was 3.9 (IQR: 3.0, 5.2) years. Two patients with abnormal TCD and normal MRA results were treated with chronic transfusion therapy. In these cases, chronic transfusion therapy was started because of recurrent acute chest syndrome (ACS) and abnormal TCD results (despite normal MRA results) respectively. Discussion: These data suggest that treatment according to the Amsterdam Protocol is a safe and efficient way to prevent primary stroke in children with SCD and to reduce exposure of these patients to long term transfusion therapy. Although the group of patients in this cohort with abnormal TCD velocities and normal MRA that did not receive transfusion therapy is limited to 12 patients with cumulative 112.0 patient-years of follow-up, we believe the results of this study are reassuring, since the cumulative incidence rate in this study is significantly lower (0.0 (95% CI: 0.0, 0.25)) compared to the incidence reported for patients with abnormal Doppler results in the original study by Adams et al. (0.4 (95% CI: 0.27, 0.59) at 30 months).(2)References 1. DeBaun et al, Blood Adv. 2020; 4(8):1554-88 2. Adams et al, Ann Neurol. 1997; 42(5):699-704